Characterization of Hypomagnesemia in Alcoholic Hepatitis Patients and Its Association with Liver Injury and Severity Markers.

INTRODUCTION: Hypomagnesemia has been documented in alcohol-associated liver disease (ALD). This study aims to characterize hypomagnesemia in alcoholic hepatitis (AH) patients and identify its response with liver injury and severity markers. MATERIALS AND METHODS: A total of 49 male and female AH patients with an age range of 27-66 years were enrolled in this study. Patients were grouped by MELD: MiAH (mild AH < 12 [n = 5]), MoAH (12 ≤ moderate AH ≤ 19 [n = 13]), and SAH (severe AH ≥ 20 [n = 31]). Patients were also evaluated by MELD grouping as non-severe (MELD ≤ 19 [n = 18]) and severe (MELD ≥ 20 [n = 31]). Data were collected on demographics (Age; BMI), drinking history (AUDIT; LTDH), liver injury (ALT; AST), and liver severity (Maddrey's DF; MELD; AST:ALT). Serum magnesium (SMg) levels were tested as SOC lab (normal ≥ 0.85 ≤ 1.10 mmol/L). RESULTS: SMg was deficient in each group; the lowest in the MoAH patients. The true positivity of SMg values were at a good performance level when compared between severe and non-severe AH patients (AUROC: 0.695, p = 0.034). We found that the SMg level < 0.78 mmol/L could predict severe AH (sensitivity = 0.100 and 1-specificity = 0.000) at this true positivity, and subsequently analyzed patients with SMg < 0.78 mmol/L (Gr.4) and ≥0.78 mmol/L (Gr.5). Between Gr.4 and Gr.5, there were clinically as well as statistically significant differences in disease severity as defined by MELD, Maddrey's DF, and ABIC scores. CONCLUSIONS: This study demonstrates the utility of SMg levels to identify AH patients who may have progressed to severe status. The extent of magnesium response in AH patients also corresponded significantly with the prognosis of liver disease. Physicians suspecting AH in patients with recent heavy drinking may use SMg as an indicator to guide further testing, referrals, or treatment.

Primary Epithelioid Angiosarcoma of the Colon With Peritoneal Carcinomatosis.

Angiosarcoma is a rare mesenchymal tissue neoplasm, typically involving lymphatic or vascular endothelial cells. The tumor can arise anywhere in the body, though it is most often found as cutaneous lesions in the head and neck region. Due to its rarity, a diagnosis can sometimes be missed, especially when the sarcoma involves an uncommon site like the gastrointestinal tract. In this case, we describe a male patient who was found to have primary epithelioid angiosarcoma of the colon. Initial biopsies with immunohistochemistry staining were weakly positive for anti-cytokeratin (CAM 5.2) and negative for SRY-Box transcription factor 10 (SOX-10) and B-cell-specific activator protein (PAX-5). He was misdiagnosed as having poorly differentiated carcinoma as a result. However, a more in-depth look at the colon specimen after tumor resection revealed CD-31 and factor VIII positivity, which established the diagnosis of epithelioid angiosarcoma of the colon. This case suggests the use of rare histopathology markers as part of the workup for colonic lesions to confirm the diagnosis, especially when tissue biopsy is limited.

Serrated polyp detection rate in colonoscopies performed by gastrointestinal fellows.

Background: Clinically significant serrated polyp detection rate (CSSDR) and proximal serrated polyp detection rate (PSDR) have been suggested as the potential quality benchmarks for colonoscopy (CSSDR = 7% and PSDR = 11%) in comparison to the established benchmark adenoma detection rate (ADR). Another emerging milestone is the detection rate of lateral spreading lesions (LSLs). Objectives: This study aimed to evaluate CSSDR, PSDR, ADR, and LSL detection rates among gastrointestinal (GI) fellows performing a colonoscopy. A secondary aim was to evaluate patient factors associated with the detection rates of these lesions. Design and Methods: A retrospective review of 799 colonoscopy reports was performed. GI fellow details, demographic data, and pathology found on colonoscopy were collected. Multiple logistic regression analysis was performed to identify the factors associated with CSSDR, PSDR, ADR, and LSL detection rates. A p value < 0.05 was considered statistically significant. Results: For our patient population, the median age was 58 years; 396 (49.8%) were male and 386 (48.6%) were African American. The 15 GI fellows ranged from first (F1), second (F2), or third (F3) year of training. We found an overall CSSDR of 4.4%, PSDR of 10.5%, ADR of 42.1%, and LSL detection rate of 3.2%. Female gender was associated with CSSDR, while only age was associated with PSDR. GI fellow level of training was associated with LSL detection rate, with the odds of detecting them expected to be four times higher in F2/F3s than F1s. Conclusion: Although GI fellows demonstrated an above-recommended ADR and nearly reached target PSDR, they failed to achieve target CSSDR. Future studies investigating a benchmark for LSL detection rate are needed to quantify if GI fellows are detecting these lesions at adequate rates.

Illustration of Gut-Thyroid Axis in Alcohol Use Disorder: Interplay of Gut Dysfunction, Pro-Inflammatory Responses, and Thyroid Function.

(1) Background: Heavy and chronic alcohol drinking leads to altered gut dysfunction, coupled with a pro-inflammatory state. Thyroid-associated hormones and proteins may be dysregulated by heavy and chronic alcohol intake; however, the mechanism for altered gut-derived changes in thyroid function has not been studied thus far. This study investigates the role of alcohol-induced gut dysfunction and pro-inflammatory cytokine profile in the thyroid function of patients with alcohol use disorder (AUD). (2) Methods: Male and female AUD patients (n = 44) were divided into Gr.1, patients with normal thyroid-stimulating hormone (TSH) levels (n = 28, 0.8 ≤ TSH ≤ 3 mIU/L); and Gr.2, patients with clinically elevated TSH levels (n = 16, TSH > 3 mIU/L). Demographics, drinking measures, comprehensive metabolic panels, and candidate thyroid markers (TSH, circulating triiodothyronine (T3), and free thyroxine (fT4)) were analyzed. Gut-dysfunction-associated markers (lipopolysaccharide (LPS), LPS-binding protein (LBP), and soluble LPS-induced pathogen-associated protein (sCD14)), and candidate pro-inflammatory cytokines (IL-1ß, TNF-α, IL-6, IL-8, MCP-1, PAI-1) were also evaluated. (3) Results: Patients in both groups presented with a borderline overweight BMI category. Gr.2 reported numerically higher indices of chronic and heavy drinking patterns than Gr.1. The fT4 levels were elevated, while T3 was within normal limits in both groups. The gut dysfunction markers LBP and sCD14 were numerically elevated in Gr.2 vs. Gr.1, suggesting subtle ongoing changes. Candidate pro-inflammatory cytokines were significantly elevated in Gr.2, including IL-1 ß, MCP-1, and PAI-1. Gr.2 showed a strong and statistically significant effect on the gut-immune-thyroid response (r = 0.896, 36 p = 0.002) on TSH levels in a multivariate regression model with LBP, sCD14, and PAI-1 levels as upstream variables in the gut-thyroid pathway. In addition, AUROC analysis demonstrated that many of the cytokines strongly predicted TSH in Gr.2, including IL-6 (area = 0.774, 39 p < 0.001) and TNF-α (area = 0.708, p = 0.017), among others. This was not observed in Gr.1. Gr.2 demonstrated elevated fT4, as well as TSH, which suggests that there was subclinical thyroiditis with underlying CNS dysfunction and a lack of a negative feedback loop. (4) Conclusions: These findings reveal the toxic effects of heavy and chronic drinking that play a pathological role in thyroid gland dysregulation by employing the gut-brain axis. These results also emphasize potential directions to carefully evaluate thyroid dysregulation in the overall medical management of AUD.

Prevalence of hepatopancreatic injury and clinical outcomes in patients with COVID-19 in USA.

BACKGROUND: (1) To determine the prevalence of hepatopancreatic injury in coronavirus disease 2019 (COVID-19) patients. (2) To correlate hepatopancreatic injury in COVID-19 with mortality, disease severity, and length of stay in this cohort. RESULTS: Forty-five thousand three hundred sixty patients were included in the analysis, 62.82% of which had either hepatic or pancreatic injury. There was a significant upward trend in transaminases, alkaline phosphatase, prothrombin time, bilirubin, lactate dehydrogenase, and lipase and a downward trend in albumin with an increase in disease severity. COVID-19-positive patients with hepato-pancreatic injury have a significantly higher mortality (OR 3.39, 95%CI 3.15-3.65) after controlling for the differences in age, sex, race/ethnicity, liver cirrhosis, and medication exposures. They also have increased disease severity (OR 2.7, 95%CI 2.5-2.9 critical vs mild/moderate; OR 1.4, 95% CI 1.3-1.5 severe vs mild/moderate) and longer hospital length of stay (2 days). CONCLUSION: COVID-19 can cause liver injury. Mortality, disease severity, and hospital length of stay are increased in COVID-19 patients with hepatopancreatic injury.

Nausea and Vomiting in 2021: A Comprehensive Update.

GOAL: A comprehensive review of treatments for nausea and vomiting (N/V). BACKGROUND: N/V are common symptoms encountered in medicine. While most cases of acute N/V related to a specific cause can be straightforward to manage, other cases of acute N/V such as chemotherapy-induced N/V and especially chronic unexplained N/V can be difficult to control, leading to a significant decline in the patient's quality of life and increased cost of medical care from repeated hospitalizations. STUDY: Traditional management has relied on pharmacotherapy which may be inadequate in a certain proportion of these patients. Many of the medications used in the management of N/V have significant side effect profiles making the need for new and improved interventions of great importance. RESULTS: This review covers a broad review of the pathophysiology of N/V, pharmacotherapy, including safety concerns and controversies with established pharmaceuticals, newer immunotherapies, bioelectrical neuromodulation (including gastric electrical stimulation), behavioral and surgical therapies, and complementary medicine. CONCLUSION: On the basis of emerging understandings of the pathophysiology of N/V, improved therapies are becoming available.

Lower Serum Magnesium Concentrations are associated With Specific Heavy Drinking Markers, Pro-Inflammatory Response and Early-Stage Alcohol-associated Liver Injury§.

AIM: Chronic heavy alcohol intake frequently causes liver inflammation/injury, and altered mineral metabolism may be involved in this liver pathology. In this study, we evaluated the association of heavy drinking, changes in serum magnesium levels and biochemical evidence of liver injury in alcohol-use-disorder (AUD) patients who had no clinical signs or symptoms of liver injury. We also aimed to identify any sex-based differences in patients with mild or no biochemical evidence of liver injury induced by heavy drinking. METHODS: 114 heavy drinking alcohol-dependent (AD) female and male patients aged 21-65 years without clinical manifestations of liver injury, who were admitted to an alcohol treatment program, were grouped by alanine aminotransaminase (ALT) levels: ≤ 40 IU/L, as no liver injury (GR.1), and ALT>40 IU/L as mild liver injury (GR.2). Patients were actively drinking until the day of admission. Comprehensive metabolic biochemistry results, fatty acid panel, serum magnesium and drinking history data were collected at admission; and study-specific measures were evaluated. RESULTS: In all AD patients, lower magnesium was significantly associated with the heavy drinking marker and heavy drinking days past 90 days (HDD90). A lower serum magnesium concentration was observed in AD patients with mild liver injury. Females of both groups had mean levels of magnesium in the deficient range. A clinically significant drop in magnesium levels was observed only in the GR.2 (mild liver injury) male AD patients. Females showed a significant association between low magnesium levels and the ω6:ω3 polyunsaturated fatty acids (PUFAs) ratio. CONCLUSIONS: Specific heavy drinking markers showed an association with lower magnesium levels. Low serum magnesium levels are common in subjects with AUD and appear to be associated with the onset of liver injury.

Flushing Disorders Associated with Gastrointestinal Symptoms: Part 1, Neuroendocrine Tumors, Mast Cell Disorders and Hyperbasophila.

Flushing is the subjective sensation of warmth accompanied by visible cutaneous erythema occurring throughout the body with a predilection for the face, neck, pinnae, and upper trunk where the skin is thinnest and cutaneous vessels are superficially located and in greatest numbers. Flushing can be present in either a wet or dry form depending upon whether neural-mediated mechanisms are involved. Activation of the sympathetic nervous system results in wet flushing, accompanied by diaphoresis, due to concomitant stimulation of eccrine sweat glands. Wet flushing is caused by certain medications, panic disorder and paroxysmal extreme pain disorder (PEPD). Vasodilator mediated flushing due to the formation and release of a variety of biogenic amines, neuropeptides and phospholipid mediators such as histamine, serotonin and prostaglandins, respectively, typically presents as dry flushing where sweating is characteristically absent. Flushing occurring with neuroendocrine tumors accompanied by gastrointestinal symptoms is generally of the dry flushing variant, which may be an important clinical clue to the differential diagnosis. A number of primary diseases of the gastrointestinal tract cause flushing, and conversely extra-intestinal conditions are associated with flushing and gastrointestinal symptoms. Gastrointestinal findings vary and include one or more of the following non-specific symptoms such as abdominal pain, nausea, vomiting, diarrhea or constipation. The purpose of this review is to provide a focused comprehensive discussion on the presentation, pathophysiology, diagnostic evaluation and management of those diseases that arise from the gastrointestinal tract or other site that may cause gastrointestinal symptoms secondarily accompanied by flushing. This review is divided into two parts given the scope of conditions that cause flushing and affect the gastrointestinal tract: Part 1 covers neuroendocrine tumors (carcinoid, pheochromocytomas, vasoactive intestinal polypeptide, medullary carcinoma of the thyroid), polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS), and conditions involving mast cells and basophils; while Part 2 covers dumping syndrome, mesenteric traction syndrome, rosacea, hyperthyroidism and thyroid storm, anaphylaxis, panic disorders, paroxysmal extreme pain disorder, and food, alcohol and medications.

Flushing Disorders Associated with Gastrointestinal Symptoms: Part 2, Systemic Miscellaneous Conditions.

Flushing disorders with involvement of the gastrointestinal tract represent a heterogeneous group of conditions. In part 1 of this review series, neuroendocrine tumors (NET), mast cell activation disorders (MCAD), and hyperbasophilia were discussed. In this section we discuss the remaining flushing disorders which primarily or secondarily involve the gastrointestinal tract. This includes dumping syndrome, mesenteric traction syndrome, rosacea, hyperthyroidism and thyroid storm, anaphylaxis, panic disorders, paroxysmal extreme pain disorder, and food, alcohol and medications. With the exception of paroxysmal pain disorders, panic disorders and some medications, these disorders presents with dry flushing. A detailed and comprehensive family, social, medical and surgical history, as well as recognizing the presence of other systemic symptoms are important in distinguishing the different disease that cause flushing with gastrointestinal symptoms.